When to Prescribe and Avoid Modafinil
FDA-Approved Indications
Modafinil should be prescribed for excessive daytime sleepiness in three specific conditions: narcolepsy, obstructive sleep apnea (as adjunct to CPAP), and shift work sleep disorder. 1
Approved Uses:
- Narcolepsy: 200 mg once daily in the morning to improve wakefulness 1
- Obstructive Sleep Apnea (OSA): 200 mg once daily in the morning, but only as adjunctive therapy—not as treatment for the underlying airway obstruction itself, and patients must continue CPAP therapy 1, 2
- Shift Work Sleep Disorder (SWD): 200 mg taken approximately one hour before the start of the work shift 1
Off-Label Palliative Care Use:
- Cancer-related fatigue with refractory daytime sedation: Modafinil is recommended as an option when methylphenidate or dextroamphetamine are insufficient 3
- Lower doses (50-200 mg/day) may be more appropriate for concentration problems and fatigue, while higher doses (200-400 mg/day) are more effective for sleepiness 4
Absolute Contraindications
Do not prescribe modafinil in the following situations:
- Known hypersensitivity to modafinil or armodafinil 1
- Pediatric patients under 17 years: Not FDA-approved due to increased risk of Stevens-Johnson syndrome 4
- Any sign of rash: Discontinue immediately unless clearly unrelated to the drug 1
Situations Requiring Extreme Caution or Avoidance
Psychiatric Conditions:
- History of psychosis, depression, or mania: Use with extreme caution and consider discontinuing if psychiatric symptoms develop 1
- Modafinil can exacerbate underlying psychiatric conditions 5
Cardiovascular Disease:
- Known cardiovascular disease: Requires increased monitoring as modafinil can increase blood pressure and heart rate 6, 1
- Clinically significant increases in blood pressure occur infrequently but warrant monitoring 7
Dermatologic Reactions:
- First sign of any rash: Stop modafinil immediately—risk of Stevens-Johnson syndrome, multi-organ hypersensitivity reactions, and angioedema 4, 1
- This risk is particularly elevated in pediatric populations 4
Hepatic Impairment:
- Severe hepatic impairment: Reduce dose to half the recommended dose (100 mg daily) 1
Geriatric Patients:
- Elderly patients: Start with lower dose of 100 mg once upon awakening, increase at weekly intervals as necessary 4
Drug Interactions:
- Steroidal contraceptives: Modafinil reduces efficacy—use alternative or additional contraception during treatment and for one month after discontinuation 1
- Cyclosporine: Blood concentrations may be reduced 1
- CYP2C19 substrates (omeprazole, phenytoin, diazepam): Exposure may be increased 1
Clinical Pearls and Common Pitfalls
Maximum Dosing:
- Never exceed 400 mg per day total dose 4
- Administer as single morning dose or divided into morning and midday doses 4
- Last dose should be no later than 2:00 PM to avoid insomnia 3
Common Adverse Effects to Monitor:
- Headache (most common), nausea, nervousness, insomnia, anxiety, back pain, dyspepsia 4, 1
- These occur in >5% of patients but are generally well-tolerated 1, 7
Important Monitoring:
- Persistent sleepiness: Assess frequently and advise patients to avoid driving or dangerous activities if sleepiness persists 1
- Blood pressure and heart rate: Monitor in all patients, especially those with cardiovascular risk factors 6
Advantages Over Traditional Stimulants:
- Lower abuse potential compared to amphetamines and methylphenidate 4, 6
- No rebound phenomena after withdrawal 8
- Does not affect sleep architecture or scheduled sleep 7, 9
When NOT to Use Modafinil
Do not use modafinil for:
- Cataplexy: Modafinil does not suppress cataplexy in narcolepsy patients 5, 8
- Primary treatment of OSA: Must be used only as adjunct to CPAP, never as replacement 1
- Uncontrolled moderate to severe hypertension 8
- Conditions with insufficient evidence: Parkinson's disease, cocaine addiction, chronic fatigue syndrome, traumatic brain injury—studies show inconsistent or no benefit beyond placebo 5